Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1

Edward C. Emery, Eleftheria Diakogiannaki, Clive Gentry, Arianna Psichas, Abdella M. Habib, Stuart Bevan, Michael J. M. Fischer, Frank Reimann, Fiona M. Gribble

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Stimulus-coupled incretin secretion from enteroendocrine cells plays a fundamental role in glucose homeostasis and could be targeted for the treatment of type 2 diabetes. Here, we investigated the expression and function of transient receptor potential (TRP) ion channels in enteroendocrine L cells producing GLP-1. By microarray and quantitative PCR analysis, we identified trpa1 as an L cell-enriched transcript in the small intestine. Calcium imaging of primary L cells and the model cell line GLUTag revealed responses triggered by the TRPA1 agonists allyl-isothiocyanate (mustard oil), carvacrol, and polyunsaturated fatty acids, which were blocked by TRPA1 antagonists. Electrophysiology in GLUTag cells showed that carvacrol induced a current with characteristics typical of TRPA1 and triggered the firing of action potentials. TRPA1 activation caused an increase in GLP-1 secretion from primary murine intestinal cultures and GLUTag cells, an effect that was abolished in cultures from trpa1(-/-) mice or by pharmacological TRPA1 inhibition. These findings present TRPA1 as a novel sensory mechanism in enteroendocrine L cells, coupled to the facilitation of GLP-1 release, which may be exploitable as a target for treating diabetes.

Original languageEnglish
Pages (from-to)1202-10
Number of pages9
JournalDiabetes
Volume64
Issue number4
DOIs
Publication statusPublished - Apr 2015

Keywords

  • Animals
  • Calcium
  • Cells, Cultured
  • Enteroendocrine Cells
  • Glucagon-Like Peptide 1
  • Intestine, Small
  • Mice
  • Mice, Knockout
  • Signal Transduction
  • Transient Receptor Potential Channels

Fingerprint

Dive into the research topics of 'Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1'. Together they form a unique fingerprint.

Cite this